Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation
Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2−/− mice contain reduced content of LDs a...
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doaj-13ce86a9cfe5451db7c927334f98c94d2021-04-29T04:37:01ZengElsevierJournal of Lipid Research0022-22752017-11-01581121472161Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidationYuan Z. Feng0Jenny Lund1Yuchuan Li2Irlin K. Knabenes3Siril S. Bakke4Eili T. Kase5Yun K. Lee6Alan R. Kimmel7G. Hege Thoresen8Arild Christian Rustan9Knut Tomas Dalen10Department of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayDepartment of Nutrition, University of Oslo, Oslo, NorwayDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayLaboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MDLaboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MDDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Pharmaceutical Biosciences, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, NorwayTo whom correspondence should be addressed.; Department of Nutrition, University of Oslo, Oslo, Norway; The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayLipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2−/− mice contain reduced content of LDs and accumulate less oleic acid (OA) in triacylglycerol (TAG) due to elevated LD hydrolysis in comparison with Plin2+/+ myotubes. The reduced ability to store TAG in LDs in Plin2−/− myotubes is accompanied by a shift in energy metabolism. Plin2−/− myotubes are characterized by increased oxidation of OA, lower glycogen synthesis, and reduced glucose oxidation in comparison with Plin2+/+ myotubes, perhaps reflecting competition between FAs and glucose as part of the Randle cycle. In accord with these metabolic changes, Plin2−/− myotubes have elevated expression of Ppara and Ppargc1a, transcription factors that stimulate expression of genes important for FA oxidation, whereas genes involved in glucose uptake and oxidation are suppressed. Loss of Plin2 had no impact on insulin-stimulated Akt phosphorylation. Our results suggest that Plin2 is essential for protecting the pool of skeletal muscle LDs to avoid an uncontrolled hydrolysis of stored TAG and to balance skeletal muscle energy metabolism.http://www.sciencedirect.com/science/article/pii/S0022227520338050Plin2triacylglycerollipid dropletlipolysis and fatty acid metabolismfatty acid/metabolisminsulin signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan Z. Feng Jenny Lund Yuchuan Li Irlin K. Knabenes Siril S. Bakke Eili T. Kase Yun K. Lee Alan R. Kimmel G. Hege Thoresen Arild Christian Rustan Knut Tomas Dalen |
spellingShingle |
Yuan Z. Feng Jenny Lund Yuchuan Li Irlin K. Knabenes Siril S. Bakke Eili T. Kase Yun K. Lee Alan R. Kimmel G. Hege Thoresen Arild Christian Rustan Knut Tomas Dalen Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation Journal of Lipid Research Plin2 triacylglycerol lipid droplet lipolysis and fatty acid metabolism fatty acid/metabolism insulin signaling |
author_facet |
Yuan Z. Feng Jenny Lund Yuchuan Li Irlin K. Knabenes Siril S. Bakke Eili T. Kase Yun K. Lee Alan R. Kimmel G. Hege Thoresen Arild Christian Rustan Knut Tomas Dalen |
author_sort |
Yuan Z. Feng |
title |
Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
title_short |
Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
title_full |
Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
title_fullStr |
Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
title_full_unstemmed |
Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
title_sort |
loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2017-11-01 |
description |
Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2−/− mice contain reduced content of LDs and accumulate less oleic acid (OA) in triacylglycerol (TAG) due to elevated LD hydrolysis in comparison with Plin2+/+ myotubes. The reduced ability to store TAG in LDs in Plin2−/− myotubes is accompanied by a shift in energy metabolism. Plin2−/− myotubes are characterized by increased oxidation of OA, lower glycogen synthesis, and reduced glucose oxidation in comparison with Plin2+/+ myotubes, perhaps reflecting competition between FAs and glucose as part of the Randle cycle. In accord with these metabolic changes, Plin2−/− myotubes have elevated expression of Ppara and Ppargc1a, transcription factors that stimulate expression of genes important for FA oxidation, whereas genes involved in glucose uptake and oxidation are suppressed. Loss of Plin2 had no impact on insulin-stimulated Akt phosphorylation. Our results suggest that Plin2 is essential for protecting the pool of skeletal muscle LDs to avoid an uncontrolled hydrolysis of stored TAG and to balance skeletal muscle energy metabolism. |
topic |
Plin2 triacylglycerol lipid droplet lipolysis and fatty acid metabolism fatty acid/metabolism insulin signaling |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520338050 |
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